The studies outlined in ths proposal are designed to gain information about the mechanisms regulating the immunological response of the lung to environmental and occupational allergens. Specifically, these studies are focused on hypersensitivity pneumonitis(HP), an allergic lung disease affecting a alveolar interstitial tissue and caused by an array of organic dusts from an increasing number of environmental and occupational sources. Pigeon breeders disease (PBD) is used as a model of HP because of the availability of a population of symptomatic and asymptomatic, but similarly exposed individuals. In addition, the source of the etiologic agent, pigeon proteins, is plentiful, easily obtained and relatively simple in composition. The approach which has been developed in these studies is based on considerable experience and past achievement. Three projects have been outlined. The first study makes use of patients with PBD and their asymptomatic counterparts. Peripheral blood and lung lavages are studied from both groups by in vitro techniques and compared. In addition, these studies are compared with similar studies in a nonhuman primate model of HP which closely resembles the human disease and where in vivo assessment of hypotheses can be carried out. The second project is concerned with two animal models of hypersensitivity lung disease in which the immunoregulatory mechanisms of acute and chronic pulmonary inflammation are probed. The goals are to define in cellular and molecular terms, the mechanisms involved in the pathogenesis of the pulmonary lesions which have been shown to be related to the human disease, HP. The final project deals with the antigens themselves. Two of the major sources of allergens causing HP are of animal and microbial origin. This project is concerned with the antigenic components of pigeon droppings (the etiologic agent of PBD) and thermophilic actinomycetes (the etiologic agent of farmers lung disease). These sources will be analyzed using biochemical and immunochemical techniques. The relevant antigens will be isolated and characterized and utilized for further studies concerning their role in disease.